5-177600183-G-T

Variant names:

• chr5-177600183-G-T
• rs562627459
• NM_007255.3:c.-28G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007255.3(B4GALT7):​c.-28G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,331,954 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (26 hom.)
• Consequence: B4GALT7 NM_007255.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.193
• Publications: 0 publications found

Genes affected

B4GALT7 (HGNC:930): (beta-1,4-galactosyltransferase 7) This gene is a member of the beta-1,4-galactosyltransferase (beta4GalT) family. Family members encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose. Each beta4GalT member has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus which then remains uncleaved to function as a transmembrane anchor. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein linkage (GlcA-beta1,3-Gal-beta1,3-Gal-beta1,4-Xyl-beta1-O-Ser) found in proteoglycans. This enzyme differs from other beta4GalTs because it lacks the conserved Cys residues found in beta4GalT1-beta4GalT6 and it is located in cis-Golgi instead of trans-Golgi. Mutations in this gene have been associated with the progeroid form of Ehlers-Danlos syndrome. [provided by RefSeq, Oct 2009]

B4GALT7 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, spondylodysplastic type, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Ehlers-Danlos syndrome, spondylodysplastic type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-177600183-G-T is Benign according to our data. Variant chr5-177600183-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 506362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00202 (307/151742) while in subpopulation SAS AF = 0.0203 (98/4826). AF 95% confidence interval is 0.0171. There are 1 homozygotes in GnomAd4. There are 166 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007255.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT7	NM_007255.3	MANE Select	c.-28G>T		5_prime_UTR	Exon 1 of 6	NP_009186.1	Q9UBV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	B4GALT7	ENST00000029410.10	TSL:1 MANE Select	c.-28G>T		5_prime_UTR	Exon 1 of 6	ENSP00000029410.5	Q9UBV7
	B4GALT7	ENST00000871348.1		c.-28G>T		5_prime_UTR	Exon 1 of 7	ENSP00000541407.1
	B4GALT7	ENST00000966184.1		c.-28G>T		5_prime_UTR	Exon 1 of 6	ENSP00000636243.1

Frequencies

GnomAD3 genomes AF: 0.00202 AC: 306 AN: 151634 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000854

Gnomad ASJ AF: 0.000867

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.000863

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00252

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00513 AC: 206 AN: 40194 AF XY: 0.00692

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000413

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.00210

Gnomad OTH exome AF: 0.00247

GnomAD4 exome AF: 0.00246 AC: 2900 AN: 1180212 Hom.: 26 Cov.: 30 AF XY: 0.00274 AC XY: 1576 AN XY: 574566

African (AFR) AF: 0.000207 AC: 5 AN: 24172

American (AMR) AF: 0.000549 AC: 9 AN: 16386

Ashkenazi Jewish (ASJ) AF: 0.000276 AC: 5 AN: 18112

East Asian (EAS) AF: 0.000262 AC: 7 AN: 26700

South Asian (SAS) AF: 0.0168 AC: 831 AN: 49564

European-Finnish (FIN) AF: 0.00127 AC: 34 AN: 26864

Middle Eastern (MID) AF: 0.00860 AC: 28 AN: 3256

European-Non Finnish (NFE) AF: 0.00190 AC: 1843 AN: 968040

Other (OTH) AF: 0.00293 AC: 138 AN: 47118

GnomAD4 genome AF: 0.00202 AC: 307 AN: 151742 Hom.: 1 Cov.: 31 AF XY: 0.00224 AC XY: 166 AN XY: 74158

African (AFR) AF: 0.000169 AC: 7 AN: 41472

American (AMR) AF: 0.000853 AC: 13 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.000867 AC: 3 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4826

European-Finnish (FIN) AF: 0.000863 AC: 9 AN: 10426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00252 AC: 171 AN: 67864

Other (OTH) AF: 0.00238 AC: 5 AN: 2102

Alfa AF: 0.000956 Hom.: 0

Bravo AF: 0.00149

Asia WGS AF: 0.00348 AC: 12 AN: 3464

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.19
PromoterAI		0.082	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs562627459; hg19: chr5-177027184;